COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure
COSMIC-HF
A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With Heart Failure and Left Ventricular Systolic Dysfunction
2 other identifiers
interventional
544
13 countries
101
Brief Summary
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2013
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 18, 2013
CompletedFirst Posted
Study publicly available on registry
February 8, 2013
CompletedStudy Start
First participant enrolled
February 26, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 22, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 19, 2015
CompletedResults Posted
Study results publicly available
May 17, 2021
CompletedAugust 12, 2021
July 1, 2021
2.4 years
January 18, 2013
April 23, 2021
July 25, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7
Day 7 at predose
Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil
Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose
Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing
Predose (before morning dose) at weeks 2, 8, 12, 16, and 20
Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil
Weeks 2 and 12 at predose and 1, 2, 4, 6, and 8 hours post-dose.
Secondary Outcomes (8)
Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20
Baseline and week 20
Expansion Phase: Change From Baseline in Stroke Volume at Week 20
Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20
Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20
Baseline and week 20
Expansion Phase: Change From Baseline in Heart Rate at Week 20
Baseline and week 20
- +3 more secondary outcomes
Study Arms (11)
Dose-escalation Cohort 1: Placebo
PLACEBO COMPARATORParticipants received placebo tablets twice a day (BID) for 7 days.
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1
EXPERIMENTALParticipants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days.
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2
EXPERIMENTALParticipants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days.
Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2
EXPERIMENTALParticipants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days.
Dose-escalation Cohort 2: Placebo
PLACEBO COMPARATORParticipants received placebo tablets twice a day for 7 days.
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1
EXPERIMENTALParticipants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days.
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2
EXPERIMENTALParticipants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days.
Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2
EXPERIMENTALParticipants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days.
Expansion Phase: Placebo
PLACEBO COMPARATORParticipants received placebo tablets twice a day for 20 weeks.
Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1
EXPERIMENTALParticipants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks.
Expansion Phase: OM M-F1 PK-based Titration
EXPERIMENTALAll participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day. At week 8 the dose escalated to 50 mg twice a day if the week 2 predose plasma concentration of OM was less than the predefined cutoff of 200 ng/mL.
Interventions
Modified release tablets for oral administration
Modified release tablets for oral administration
Modified release tablets matching to omecamtiv mecarbil
Modified release tablets for oral administration
Eligibility Criteria
You may qualify if:
- History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
- Treated with stable, optimal pharmacological therapy for ≥ 4 weeks
- History of left ventricular ejection fraction (LVEF) ≤ 40%
- Elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP)
You may not qualify if:
- Severe uncorrected valvular heart disease
- Hospitalization within 30 days prior to enrollment
- Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease
- Acute myocardial infarction, unstable angina or persistent angina at rest within 30 days prior to randomization
- Systolic blood pressure \> 160 mmHg or \< 90 mmHg or diastolic blood pressure \> 90 mmHg
- Total bilirubin ≥ 2 x upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x ULN
- Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\^2
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cytokineticslead
Study Sites (101)
Research Site
Mobile, Alabama, 36608, United States
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Costa Mesa, California, 92626, United States
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Fresno, California, 93721, United States
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Inglewood, California, 90301, United States
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La Jolla, California, 92037, United States
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Los Angeles, California, 90033, United States
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Thousand Oaks, California, 91360, United States
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Tustin, California, 92780, United States
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Danbury, Connecticut, 06810, United States
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Newark, Delaware, 19718, United States
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Atlantis, Florida, 33462, United States
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Aventura, Florida, 33180, United States
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Clearwater, Florida, 33756, United States
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Miami, Florida, 33136, United States
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Tampa, Florida, 33606, United States
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Atlanta, Georgia, 30322, United States
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Macon, Georgia, 31201, United States
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Chicago, Illinois, 60612, United States
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Auburn, Maine, 04210, United States
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Baltimore, Maryland, 21201, United States
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Detroit, Michigan, 48202, United States
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Petoskey, Michigan, 49770, United States
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Minneapolis, Minnesota, 55415, United States
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Minneapolis, Minnesota, 55417, United States
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St Louis, Missouri, 63110, United States
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Las Vegas, Nevada, 89128, United States
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Cortlandt Manor, New York, 10567, United States
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The Bronx, New York, 10467, United States
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Chapel Hill, North Carolina, 27599, United States
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Durham, North Carolina, 27705, United States
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Oklahoma City, Oklahoma, 73120, United States
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Portland, Oregon, 97239, United States
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Greenville, South Carolina, 29605, United States
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Nashville, Tennessee, 37232-8802, United States
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Tullahoma, Tennessee, 37388, United States
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Houston, Texas, 77030, United States
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Seattle, Washington, 98195, United States
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Madison, Wisconsin, 53792, United States
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Darlinghurst, New South Wales, 2010, Australia
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Nedlands, Western Australia, 6009, Australia
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Antwerp, 2020, Belgium
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Bonheiden, 2820, Belgium
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Ghent, 9000, Belgium
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Ieper, 8900, Belgium
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Liège, 4000, Belgium
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Kazanlak, 6100, Bulgaria
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Pazardzhik, 4700, Bulgaria
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Plovdiv, 4002, Bulgaria
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Sandanski, 2800, Bulgaria
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Sliven, 8800, Bulgaria
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Smolyan, 4400, Bulgaria
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Sofia, 1527, Bulgaria
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Edmonton, Alberta, T6G 2B7, Canada
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Winnipeg, Manitoba, R2H 2A6, Canada
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St. John's, Newfoundland and Labrador, A1B 3V6, Canada
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Halifax, Nova Scotia, B3H 3A7, Canada
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Ottawa, Ontario, K1Y 4W7, Canada
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Montreal, Quebec, H3G 1A4, Canada
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Québec, Quebec, G1V 4G5, Canada
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Sherbrooke, Quebec, J1G 2E8, Canada
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Trois-Rivières, Quebec, G8T 7A1, Canada
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Brno, 625 00, Czechia
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Brno, 636 00, Czechia
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Olomouc, 771 11, Czechia
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Prague, 128 08, Czechia
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Prague, 140 21, Czechia
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Svitavy, 568 25, Czechia
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Teplice, 415 29, Czechia
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Bad Krozingen, 79189, Germany
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Bad Nauheim, 61231, Germany
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Berlin, 13353, Germany
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Dortmund, 44137, Germany
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Greifswald, 17475, Germany
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Budapest, 1027, Hungary
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Budapest, 1125, Hungary
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Budapest, 1135, Hungary
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Jászberény, 5100, Hungary
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Zalaegerszeg, 8900, Hungary
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Brescia, 25125, Italy
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Pavia, 27100, Italy
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Verona, 37134, Italy
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Kaunas, 50009, Lithuania
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Vilnius, 08661, Lithuania
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Amersfoort, 3813 TZ, Netherlands
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Groningen, 9713 GZ, Netherlands
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Utrecht, 3584 CX, Netherlands
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Bialystok, 15-276, Poland
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Krakow, 31-202, Poland
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Krakow, 31-501, Poland
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Kłodzko, 57-300, Poland
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Lublin, 20-954, Poland
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Ruda Śląska, 41-703, Poland
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Warsaw, 04-256, Poland
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Wroclaw, 50-981, Poland
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Dudley, DY1 2HQ, United Kingdom
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Dundee, DD1 9SY, United Kingdom
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Glasgow, G11 6NT, United Kingdom
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Harrow, HA1 3UJ, United Kingdom
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Leicester, LE3 9QP, United Kingdom
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Liverpool, L14 3PE, United Kingdom
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London, EC1M 6BQ, United Kingdom
Related Publications (4)
Teerlink JR, Felker GM, McMurray JJ, Solomon SD, Adams KF Jr, Cleland JG, Ezekowitz JA, Goudev A, Macdonald P, Metra M, Mitrovic V, Ponikowski P, Serpytis P, Spinar J, Tomcsanyi J, Vandekerckhove HJ, Voors AA, Monsalvo ML, Johnston J, Malik FI, Honarpour N; COSMIC-HF Investigators. Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016 Dec 10;388(10062):2895-2903. doi: 10.1016/S0140-6736(16)32049-9. Epub 2016 Dec 1.
PMID: 27914656BACKGROUNDBiering-Sorensen T, Minamisawa M, Liu J, Claggett B, Papolos AI, Felker GM, McMurray JJV, Legg JC, Malik FI, Honarpour N, Kurtz CE, Teerlink JR, Solomon SD. The effect of the cardiac myosin activator, omecamtiv mecarbil, on right ventricular structure and function in chronic systolic heart failure (COSMIC-HF). Eur J Heart Fail. 2021 Jun;23(6):1052-1056. doi: 10.1002/ejhf.2181. Epub 2021 May 5. No abstract available.
PMID: 33826209DERIVEDBiering-Sorensen T, Minamisawa M, Claggett B, Liu J, Felker GM, McMurray JJV, Malik FI, Abbasi S, Kurtz CE, Teerlink JR, Solomon SD. Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Ventricular Myocardial Deformation in Chronic Heart Failure: The COSMIC-HF Trial. Circ Heart Fail. 2020 Dec;13(12):e008007. doi: 10.1161/CIRCHEARTFAILURE.120.008007. Epub 2020 Nov 12. No abstract available.
PMID: 33176443DERIVEDFelker GM, Solomon SD, McMurray JJV, Cleland JGF, Abbasi SA, Malik FI, Zhang H, Globe G, Teerlink JR; COSMIC-HF Investigators. Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study. Circ Heart Fail. 2020 Dec;13(12):e007814. doi: 10.1161/CIRCHEARTFAILURE.120.007814. Epub 2020 Nov 12.
PMID: 33176437DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 18, 2013
First Posted
February 8, 2013
Study Start
February 26, 2013
Primary Completion
July 22, 2015
Study Completion
August 19, 2015
Last Updated
August 12, 2021
Results First Posted
May 17, 2021
Record last verified: 2021-07